Effect of voluntary exercise on longevity of rats

The purpose of this study was to obtain information regarding the effects of exercise on longevity in rats. The exercise used was voluntary activity wheel running. The runners gradually decreased their running from approximately 4 to approximately 1 mile/day as they aged from 9 to 30 mo. The runners lived slightly but significantly longer than sedentary freely eating controls and sedentary pair-fed controls (1,012 +/- 138 vs. 923 +/- 160 and 928 +/- 186 days) but significantly less long than food-restricted paired-weight sedentary controls (1,113 +/- 150 days). Although the exercise improved survival, it did not result in an extension of life-span. In contrast, the food-restricted paired-weight sedentary rats showed a true increase in life-span. The paired-weight rats also had a significantly reduced incidence of malignancies compared with the other three groups. However, there was no significant difference between the runners and the freely eating or pair-fed sedentary controls in the cause of death. These results provide evidence that exercise improves survival but does not result in an extension of life-span in rats.     

Protein synthesis and antioxidant capacity in aging mice: effects of long-term voluntary exercise

Exercise increases metabolic rate and the production of reactive oxygen species (ROS) but also elevates protein turnover. ROS cause damage to macromolecules (e.g., proteins) and thereby contribute to aging. Protein turnover removes and replaces damaged proteins. The balance between these two responses may underlie beneficial effects of physical activity on aging. Effects of lifelong exercise on antioxidant enzyme activities and fractional synthesis rate of protein (FSRP) were examined at various ages (2-26 mo) in heart, liver, and muscle of mice that had been selectively bred for high wheel-running activity, housed with (S+) or without (S-) a running wheel, and their random-bred controls (C+) housed with running wheels. FSRP decreased with age and increased in muscle of young, but not old, activity-selected mice. Enzyme activity of superoxide dismutase and glutathione peroxidase decreased with age and showed a peak at 10 mo of age in liver. Selection for wheel-running activity did not affect antioxidant enzyme activity. Daily energy expenditure correlated positively with antioxidant levels in liver. This might indicate that oxidative stress (ROS production) increases with metabolic rate, driving upregulation of antioxidant enzymes. Alternatively, the elevated energy expenditure may reflect the energetic cost of elevated protection, consistent with the disposable-soma hypothesis and with other studies showing positive links between energy expenditure and life span. Long-term elevations in voluntary exercise did not result in elevations in antioxidant enzyme activities or protein synthesis rates.     

Selenium deficiency, endurance exercise capacity, and antioxidant status in rats

Increased O2 metabolism imposed by physical exercise is likely to augment the production of active O2 species that have been shown to react with lipids, proteins, and DNA. Antioxidants and antioxidant enzymes, such as the selenium enzyme glutathione peroxidase, minimize or prevent such potentially toxic reactions. This study shows that selenium deficiency decreases glutathione peroxidase activity in liver and muscle (less than 80%, P less than 0.001), increases total glutathione in liver, muscle, and plasma (P less than 0.05) and increases muscle cytochrome oxidase activity, and ubiquinone content (P less than 0.05) but has no effect on endurance capacity. Exercise to exhaustion resulted in a significant (P less than 0.001) elevation of total and oxidized glutathione (GSSG) and a significant (P less than 0.05) decrease of vitamin E in plasma of control and selenium-deficient rats. Acute exercise also increased tissue GSSG levels in both control and selenium-deficient groups of rats. Hence, despite a large depletion of selenium-deficient glutathione peroxidase, pronounced oxidation of glutathione to GSSG can be produced by the increased oxidative metabolism during physical exercise. The results suggest that the residual glutathione peroxidase activity is sufficient to detoxify hydroperoxides in exercising selenium-deficient animals and to prevent the impairment of endurance capacity.     

The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats

The effect of exercise on oxidant stress and on alterations in antioxidant defense in elderly has been investigated extensively. However, the impact of regularly performed long-term physical activity starting from adulthood and prolonged up to the old age is not yet clear. We have investigated the changes in the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) - and lipid peroxidation in various tissues of rats which had performed (old-trained) or had not performed (old-control) regular swimming exercise for one year. These animals were compared with young-sedentary rats. Increased lipid peroxidation was observed with ageing in all tissues (heart, liver, kidney, striated muscle) and swimming had no additional effect on this elevation of lipid peroxidation. Heart and striated muscle SOD activites, and striated muscle CAT activity increased as a consequence of ageing, whereas kidney and liver CAT activities, as well as GPx activities in kidney, liver, lung and heart were significantly decreased compared to young controls. Lung and heart SOD, liver CAT activities as well as GPx activities in liver, lung and heart were increased significantly in rats which performed exercise during ageing, compared to the old-control group. These findings suggest that lifelong exercise can improve the antioxidant defense in many tissues without constituting any additional oxidant stress.     

Effect of regular voluntary exercise on resting cardiovascular responses in SHR and WKY pregnant rats.

The purpose of this study was to assess the influence of regular voluntary exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure in the resting conscious condition and 2) fetal number, fetal weight, and number of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and experiments were conducted on gestational day 17. Resting blood flow (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured. No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8 ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among the groups. Exercise altered the relationship between maternal placental and uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher placental and uterine blood flow after training. Before gestation ESHRs ran on average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/- 4). Succinate dehydrogenase activity was higher in the white vastus lateralis (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of voluntary and forced exercise on lordosis behavior in female rats

We measured sexual behavior (lordosis) in ovariectomized, steroid-treated, exercising female rats. When estradiol-treated animals exercised voluntarily, lordosis was directly related to the amount of exercise. Forced exercise (swimming) following treatment with estradiol 17 beta and progesterone significantly increased lordosis scores but only after animals swam for 2.5 hr per day. Lordosis behavior returned to baseline levels 7 weeks after forced exercise was stopped. Circulating levels of estrogen and progesterone measured immediately after behavioral testing did not differ between animals forced to exercise and their controls. The mechanisms responsible for the increase in lordosis behavior following exercise are unclear. It is possible that a change in body composition, a change in neural sensitivity to gonadal steroids, and/or changes in pituitary or adrenal function contribute to the increased lordosis behavior in exercised animals.     

Role of exercise and ascorbate on plasma antioxidant capacity in thoroughbred race horses

During exercise, the oxygen consumption and the production of free radicals increase and can lead to oxidative stress with a deleterious effect on cellular structures involved in physical activity. To evaluate the oxidative stress produced by exercise and the role of ascorbate as an antioxidant, venous blood samples were obtained from 44 thoroughbred racehorses, before and after a 1000+/-200-m race at maximum velocity. Fourteen of these horses were treated intravenously with 5 g of ascorbate before running. Antioxidant capacity (PAOC), endogenous and exogenous ascorbate concentration, total antioxidant reactivity (TAR), urate concentration, creatine kinase activity, protein concentration and thiobarbiturate reactive substances (TBAR) as oxidative stress indicators were measured in the plasma of some of these horses. PAOC, TAR and TBAR increased after the race, while plasma ascorbate and urate concentrations remained unchanged. Total plasma protein (TPP) concentrations increased in line with antioxidant capacity. As predicted, both the plasma ascorbate concentration and PAOC increased immediately after ascorbate administration, but was not modified after the race, such as TBAR. However, in both groups plasma creatine kinase activity increased after the race. These results would suggest that the administration of ascorbate could nullify the oxidative stress produced by exercise in thoroughbred racehorses, but could not prevent muscular damage.     

Effects of voluntary resistance exercise on heme biosynthesis in rats given glucocorticoid-injections

To identify the effects of a tower-climbing exercise on bone marrow heme biosynthesis and hematological status in rats given glucocorticoid-injections as a model of aging, 29 male Sprague-Dawley rats, 10 weeks of age, were assigned to three groups: a saline control (C, n = 9), a glucocorticoid-sedentary (GS, n = 10) group, and a glucocorticoid-exercise (GE, n = 10) group. The GS and GE groups were given 2 mg/kg prednisolone daily, and the C group was given 2 ml of saline daily, subcutaneously. Each group was meal-fed commercial rat chow isoenergetically and given free access to water for 8 weeks. The GE group were allowed to climb a 200-cm tower to drink water from a bottle set at the top of it. Weight gain during the 8-week experimental period was greater in the C group than in the GS and GE groups. The gastrocnemius and tibialis anterior muscles were heavier in the C group than in other groups. The hematological parameters were not influenced by glucocorticoid administration with or without climbing exercise. Bone marrow delta-aminolevulinic acid dehydratase activity was significantly higher in the GE group than in the C group. These results suggest that 8 weeks of climbing exercise increases heme biosynthesis without alteration of hematological status in rats given glucocorticoid-injections. Resistance exercise may be a preventive therapy for iron-deficiency anemia associated with aging.     

Relation between voluntary physical activity and oxidant/antioxidant status in rats

The relationship between voluntary distance running and antioxidant capacity was studied in rats after three weeks voluntary running. Hydroxyl radical level, reduced glutathione level, activities of glutathione reductase and superoxide dismutase were measured in plasma, liver, brain, soleus and gastrocnemius white muscle. Hydroxyl radical level of liver negatively correlated with the running distance (r=-0.616, P<0.001). The reduced glutathione levels of liver and brain increased depending on the running distance and the correlation was confirmed between them in liver (r=0.638, P<0.01) and brain (r=0.766, P<0.001). The hydroxyl radical level in liver positively correlated with the activities of glutathione reductase (r=0.464, P<0.05) and superoxide dismutase (r=0.549, P<0.05). A significant positive correlation was detected between the hydroxyl radical level and superoxide dismutase activity in brain (r=0.488, P<0.05). These results demonstrate that physical activity correlates well with glutathione level and anti-oxidant enzyme activities in liver, suggesting a close relation between physical activity and induction of antioxidant systems.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes. Abstract of the study was presented at the conference Trace Elements in Men and Animals-11. June 2–6, 2002; Dr. Naziroğlu has been awarded a TEMA11 Investigative Scientist Award.     

Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control Sprague-Dawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension.     

Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.     

Effect of mild-to-moderate airflow limitation on exercise capacity

To determine the effect of mild-to-moderate airflow limitation on exercise tolerance and end-expiratory lung volume (EELV), we studied 9 control subjects with normal pulmonary function [forced expired volume in 1 s (FEV1) 105% pred; % of forced vital capacity expired in 1 s (FEV1/FVC%) 81] and 12 patients with mild-to-moderate airflow limitation (FEV1 72% pred; FEV1/FVC % 58) during progressive cycle ergometry. Maximal exercise capacity was reduced in patients [69% of pred maximal O2 uptake (VO2max)] compared with controls (104% pred VO2max, P less than 0.01); however, maximal expired minute ventilation-to-maximum voluntary ventilation ratio and maximal heart rate were not significantly different between controls and patients. Overall, there was a close relationship between VO2max and FEV1 (r2 = 0.62). Resting EELV was similar between controls and patients [53% of total lung capacity (TLC)], but at maximal exercise the controls decreased EELV to 45% of TLC (P less than 0.01), whereas the patients increased EELV to 58% of TLC (P less than 0.05). Overall, EELV was significantly correlated to both VO2max (r = -0.71, P less than 0.001) and FEV1 (r = -0.68, P less than 0.001). This relationship suggests a ventilatory influence on exercise capacity; however, the increased EELV and associated pleural pressures could influence cardiovascular function during exercise. We suggest that the increase in EELV should be considered a response reflective of the effect of airflow limitation on the ventilatory response to exercise.     

Effect of the time of day on central and peripheral fatigue during 2-min maximal voluntary contractions in persons with multiple sclerosis: gender differences

There is a lack of data on fatigue changes within 24 h among patients with multiple sclerosis. The purpose of this study was to evaluate the effect of time of day on central and peripheral fatigue during a continuous 2-min maximal voluntary contraction of the quadriceps muscle in women and men with multiple sclerosis (MS). We studied age-matched MS patients (range, 40–50 years). The inclusion criteria for patients were: a Kurtzke Expanded Disability Status score and a Fatigue Severity Scale score. We found a significant gender difference in central activation ratio (CAR) in the evening. At the end of the 2-min maximal voluntary contraction (MVC), the voluntary torque decreased by about 65% in men and women with MS in both the morning and evening. We also observed that, in women, CAR decreased markedly during the first 30 s in the evening test. The most interesting finding of our study is that central fatigue increased, whereas peripheral fatigue decreased markedly in the evening only in women. It remains unclear why women’s central fatigue is greater in the evening than in the morning.     

Oral testosterone self-administration in male hamsters: dose-response, voluntary exercise, and individual differences

Although testosterone was declared a controlled substance in 1990, the potential for steroid dependence is largely unexplored. The present study used food-induced drinking with oral testosterone self-administration in hamsters to determine (1) the dose-response for testosterone reward, (2) links between testosterone self-administration and voluntary exercise, and (3) factors predicting individual differences in androgen intake. Testosterone (1-4 mg/ml) was presented in aqueous solution 3 h/day for 35 days, with and without food. At 3 mg/ml, testosterone maintained fluid intake, even without food (3.0 +/- 0.2 ml/3h). At 4 mg/ml, fluid intake declined to 2.4 +/- 0.3 ml/3h in the presence of food. However, no dose-response relationship between testosterone self-administration and reward was observed. To test the interaction of testosterone and exercise, males drinking testosterone (RUN + T) or vehicle received a running wheel. Additional males self-administered testosterone without exercise. Testosterone intake correlated positively with exercise and negatively with body weight in RUN + T males. Experiment 3 determined the relationship between testosterone self-administration and mating or saccharin preference. There were no statistically significant correlations. However, testosterone self-administration increased mating behavior. These data demonstrate that testosterone is a mild reinforcer. Although preference for androgens is not predicted by mating or saccharin intake, testosterone intake is linked with voluntary exercise.